Hate to be blunt here, but yes. The fact that you're putting ~$10,000 into an 1800 dollar truck.

Is the speedo electronic or mechanical? if mechanical, you're good as long as you buy the right version of the tranny, some of the earlier ones I think still had a mechanical gear driving the speedo. I'd be curious how you get the rest of the gauges to work...

You're also gonna need the y pipe at the very least if not the full exhaust. that 5.0 will move a lot more air than the 4.2.

Does the V6 have the 8.8 underneath? I know the new mustangs are still sporting the old trusty 8.8, but gotta keep in mind, those are geared way steeper and are lighter; putting 400hp thru an 8.8 with crappy gearing will be rough on it.

Another thing to consider, the 4R transmissions aren't anything to write home about when it comes to efficiency or gearing. I'd research what it'll take to put in a manual in if I were you. The 6 speed from a superduty should bolt up to the 5.0 if it has the same pattern as a 4.6/5.4/6.8; but you might have to clearance the trans tunnel and/or fab up a cross member. It would hold up to anything the 5.0 can dish out and then some though.